A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle

Maclennan, P. A.; Brown, RA; Rennie, Michael J.

doi:10.1016/0014-5793(87)80139-4

Cited by 273 publications

(90 citation statements)

References 13 publications

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“…The changes in muscle amino acids noted here, i.e., increased tissue concentrations of tyrosine, phenylalanine and 3-MH and reduced levels of glutamine, together with increased urinary 3-MH/creatinine ratio, support the concept that the septic patients were in a catabolic state. In several previous reports, increased muscle protein breakdown rates were associated with, and perhaps caused by reduced intracellular glutamine levels (33,34). Tyrosine and phenylalanine are not synthesized or metabolized in skeletal muscle.…”

Section: Discussionmentioning

confidence: 87%

Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle.

Tiao¹,

Hobler²,

Wang³

et al. 1997

J. Clin. Invest.

236

104

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Previous studies provided evidence that sepsis-induced muscle proteolysis in experimental animals is caused by increased ubiquitin-proteasome-dependent protein breakdown. It is not known if a similar mechanism accounts for muscle proteolysis in patients with sepsis. We determined mRNA levels for ubiquitin and the 20 S proteasome subunit HC3 by Northern blot analysis in muscle tissue from septic ( n ϭ 7) and non-septic ( n ϭ 11) patients. Plasma and muscle amino acid concentrations and concentrations in urine of 3-methylhistidine (3-MH), creatinine, and cortisol were measured at the time of surgery to assess the catabolic state of the patients. A three-to fourfold increase in mRNA levels for ubiquitin and HC3 was noted in muscle tissue from the septic patients concomitant with increased muscle levels of phenylalanine and 3-MH and reduced levels of glutamine. Total plasma amino acids were decreased by ‫ف‬ 30% in the septic patients. The 3-MH/creatinine ratio in urine was almost doubled in septic patients. The cortisol levels in urine were higher in septic than in control patients but this difference did not reach statistical significance. The results suggest that sepsis is associated with increased mRNAs of the ubiquitin-proteasome pathway in human skeletal muscle. ( J. Clin. Invest. 1997. 99:163-168.)

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Section: Discussionmentioning

confidence: 87%

Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle.

Tiao¹,

Hobler²,

Wang³

et al. 1997

J. Clin. Invest.

236

104

View full text Add to dashboard Cite

show abstract

“…This fact makes it dif®cult to understand the uptake of Glu and Asp in spite of their decreased availability. The possible role of Gln in the steady-state of the free amino acid concentration, 24 the possible anabolic effects of Gln in the protein synthesis 30 and the hypothesized muscle mechanisms that regulate the Gln synthesis in order to maintain an elevated intracellular concentration 31 hinder the interpretation of the possible interrelationship between catabolic and anabolic pathways. Furthermore, the Gln released by muscle can be actively taken up by the small intestine as previously described.…”

Section: Discussionmentioning

confidence: 99%

Muscle amino acid pattern in obese rats

et al. 1997

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OBJECTIVE: To determine how the ability of skeletal muscle to manage amino acids is conditioned by obesity. The test was performed in two different models of obese rats: diet-obese rats and genetically obese rats. SUBJECTS: Lean and genetically obese (fa/fa) male Zucker rats were used. DESIGN: For up to 60 d of life lean animals were fed with standard chow pellet or with a hypercaloric cafeteria diet. Genetically obese rats were fed with standard chow pellet during the same period. MEASUREMENTS: Amino acid concentration in the femoral artery and vein and leg blood¯ow were measured. Free amino acid concentration, protein and nitrogen content and enzyme activities were determined in whole leg muscle. RESULTS: Amino acid availability was increased in diet-obese animals and remained unchanged in the genetically obese group. The genetically obese groups had a lower protein content and unchanged concentration of amino acids in leg muscle. Furthermore, total nitrogen remained unchanged in these animals and they showed an increased activity in alanine aminotransferase and glutamine synthetase. The leg muscle of the diet-obese rats took up several amino acids (Ala, Arg and Val) or released others (mainly Gln and Gly). Conversely, genetically obese rats took up many amino acids and did not release any. CONCLUSIONS: We conclude that in nutritionally obese rats there is an increased availability of amino acids in skeletal muscle. This augmented availability propitiates the increase in the uptake of many amino acids. In genetically obese rats, the lack of variation in amino acid availability points to a possible hereditary alteration that increases the capacity of different amino acid transport systems. Furthermore, the diminished protein content of fa/fa muscle is not due to a lower availability and intracellular pool of amino acids.

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“…Since these studies have been performed in the postpubertal male after years of exposure to their endogenous sex hormones, it is difficult to extend their physiological implications to the events at pu- berty, when the body is exposed to androgenic hormones after more than a decade ofvery low exposure. Recent animal experiments have revealed a strong correlation between the size of the muscle free glutamine pool (the most abundant amino acid in the body) and the rate of protein synthesis in vivo ( 18,19). Other studies suggest that glutamine per se may stimulate protein synthesis, and that the size of the available free glutamine pool in muscle may be an index of protein accretion (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone.

Mauras¹,

Haymond²,

Vieira³

et al. 1994

J. Clin. Invest.

101

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We investigated the effects of 4-6-wk administration of testosterone on calcium and protein metabolism in six healthy prepubertal short boys (mean age±SE = 12.9±0.6 yr). At baseline, subjects received a 4-h infusion of L-1l-'3Clleucine and L-12-'5Njglutamine, and were given 42Ca intravenously, and 'Ca PO. Testosterone enanthate ( -3 mg/ kg) was given I.M. 2 wk apart (two doses n = 5, three doses n = 1), and the study was repeated 4-5 d after the last injection.After testosterone therapy, there were significant increases in serum testosterone and mean peak and total growth hormone concentrations. Net calcium absorption (Va) and retention ( Vbal) also increased ( Va 13.3±2.3 vs 21.5±23; mg.kg-' * d-l, Vbal 8.0±2.1 vs 16.6±2.5, mg * kg-' -d-l, P < .05 both), as well as Ca's net forward flow into bone and total exchangeable pool (16 and 20%, respectively). The rate of appearance of leucine (an indicator of proteolysis) increased by 17.6±5.9%, P = 0.036. Leucine oxidation decreased by 48.6±8.0%, P = 0.004; thus, nonoxidative leucine disappearance, which estimates protein synthesis, increased significantly by 34.4±7.7%, P = 0.009. Glutamine's rate of appearance also increased (+32%), mostly through enhanced glutamine de novo synthesis (+42%).In conclusion, short term testosterone administration significantly increases calcium's retention and net forward flow into bone in prepubertal humans, as well as whole body estimates of protein and calcium anabolism. These effects may represent a pure androgen effect, an amplification of growth hormone's action or some combination of these factors. (J. Clin. Invest.

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A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle

Cited by 273 publications

References 13 publications

Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle.

Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle.

Muscle amino acid pattern in obese rats

Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone.

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